Overview

A Study of Ibrutinib + Obinutuzumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Status:
Active, not recruiting
Trial end date:
2023-07-01
Target enrollment:
0
Participant gender:
All
Summary
This research study is evaluating a combination of two drugs, ibrutinib and obinutuzumab, as a possible treatment for Chronic Lymphocytic Leukemia (CLL).
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Dana-Farber Cancer Institute
Collaborator:
Genentech, Inc.
Treatments:
Obinutuzumab
Criteria
Inclusion criteria:

- Must have a confirmed diagnosis of Chronic Lymphomcytic Leukemia or Small Lymphocytic
Lymphoma as per IW-CLL 2008 criteria and require therapy based on meeting at least one
of the following criteria:

- Evidence of progressive marrow failure with anemia (hemoglobin <11.0 g/L) and/or
thrombocytopenia (platelets <100 x 10^9/L)

- Massive (≥6 cm below the left costal margin), progressive, or symptomatic
splenomegaly

- Massive nodes (at least 10 cm longest diameter), progressive, or symptomatic
lymphadenopathy

- Progressive lymphocytosis with an increase of more than 50% over a 2-month period
or LDT of <6 months.

- Autoimmune anemia and/or thrombocytopenia that is poorly responsive to
corticosteroids

- Constitutional symptoms, defined as 1 or more of the following:

- unintentional weight loss >10% within 6 months prior to screening

- significant fatigue (inability to work or perform usual activities) fevers
>100.5° F or 38.0° C for 2 or more weeks prior to screening without evidence
of infection

- night sweats for more than 1 month prior to screening without evidence of
infection

- Relapsed after or refractory to at least one prior Chronic Lymphomcytic
Leukemia-directed therapy

- Age greater than or equal to 18 years

- ECOG Performance Status <2

- Heme criteria at screening, unless significant bone marrow involvement of Chronic
Lymphomcytic Leukemia confirmed on biopsy:

- Absolute Neutrophil Count (ANC) ≥500 cells/mm3 (0.5 x 10^9/L). Growth factor
allowed to achieve

- Platelet count ≥25,000 cells/mm3 (25 x 10^9/L) independent of transfusion within
7 days of screening

- Adequate hepatic function defined as: AST and ALT ≤ 4.0 x upper limit of normal (ULN),
bilirubin ≤2.0 x upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's
syndrome)

- Adequate renal function defined by serum creatinine <2.0 x upper limit of normal (ULN)
unless due to biopsy proven Chronic Lymphomcytic Leukemia kidney infiltration

- Women of child-bearing potential and men must agree to use adequate contraception

- Patients who have undergone prior allo transplant are eligible provided that their
transplant day 0 is > 6 months from their first dose of study drug

Exclusion Criteria:

- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

- Prior treatment with either obinutuzumab or ibrutinib

- History of other malignancies, except:

- Malignancy treated with curative intent and with no known active disease present
for ≥3 years before the first dose of study drug and felt to be at low risk for
recurrence by treating physician.

- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease.

- Adequately treated carcinoma in situ without evidence of disease.

- Low-risk prostate cancer on active surveillance

- Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc.,
or chronic administration of >20 mg/day of prednisone) within 28 days of the first
dose of study drug.

- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.

- Recent infection requiring systemic treatment that was completed ≤7 days before the
first dose of study drug.

- Known bleeding disorders or hemophilia.

- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.

- Known history of HIV or active hepatitis C virus (HCV) or hepatitis B virus (HBV).

- Any uncontrolled active systemic infection.

- Major surgery within 4 weeks of first dose of study drug.

- Currently active, clinically significant cardiovascular disease, such as uncontrolled
arrhythmia or Class 3 or 4 CHF as defined by the NYHA Functional Classification; or a
history of Myocardial Infarction, unstable angina, or acute coronary syndrome within 6
months prior to randomization.

- Lactating or pregnant.

- Patients receiving any other study agents

- Patients with known Central Nervous System involvement

- Baseline QT Interval Corrected by the Fridericia Correction Formula (QTcF) >480 ms
unless Left Bundle Branch Block

- Patients who require warfarin or other vitamin K antagonists for anticoagulation

- Concurrent administration of strong inhibitors or inducers of CYP3A